Disease relevance of GPR39

• Therefore, we evaluated the actual presence of GPR39 mRNA in human adipose tissue and whether GPR39 expression levels are altered in obesity and obesity-associated T2DM [1].
• The obestatin receptor (GPR39) is expressed in human adipose tissue and is down-regulated in obesity-associated type 2 diabetes mellitus [1].

High impact information on GPR39

• Antibody feeding experiments demonstrated that the epitope-tagged ghrelin receptor was constitutively internalized but could be trapped at the cell surface by an inverse agonist, whereas GPR39 remained at the cell surface [2].
• GPR39 displayed a clear but lower degree of constitutive activity through the inositol phosphate and cAMP response element pathways [2].
• In contrast, GPR39 signaled with the highest constitutive activity in respect of activation of serum response element-dependent transcription, in part, possibly, through G(12/13) and Rho kinase [2].
• Although Zn(2+) stimulated inositol phosphate turnover, cAMP production, arrestin mobilization, as well as cAMP response element-dependent and serum response element-dependent transcriptional activity in GPR39-expressing cells as opposed to mock-transfected cells, no reproducible effect was obtained with obestatin in the GPR39-expressing cells [3].
• In contrast, the potency and efficacy of Zn(2+) in respect of activating signaling indicates that this metal ion could be a physiologically relevant agonist or modulator of GPR39 [3].

Biological context of GPR39

• GPR38 and GPR39 share significant amino acid sequence identity with the GHS-R and NT-Rs 1 and 2 [4].
• Fluorescence in situ hybridization localized the genes for GPR38 and GPR39 to separate chromosomes, distinct from the gene encoding the GHS-R and NT-R type 1 [4].
• Three FMs GPR38, GPR39 and FM3 were isolated from human genomic libraries [5].
• The reduced expression levels of GPR39 in omental adipose tissue observed in obese patients with T2DM suggest an involvement of obestatin signalling in glucose homeostasis and T2DM development [1].
• We could, however, not demonstrate activation of the GPR39 receptor by obestatin via any of these signal transduction pathways [6].

Anatomical context of GPR39

• By quantitative PCR analysis, GPR39 expression was readily detected in peripheral organs such as duodenum and kidney but not in the pituitary and hypothalamus, i.e. presumed central target organs for obestatin [3].
• Conclusion GPR39 is expressed in human adipose tissue [1].
• The obestatin receptor GPR39 is present in brain and pituitary gland [7].
• Overall, we observed a greater gene-silencing efficiency on the MGC29643 transcript than on the GPR39 transcript in HeLa cells [8].

Associations of GPR39 with chemical compounds

• We could activate GPR39 by high concentrations of Zn(2+), demonstrating cell surface expression of a functional receptor that could elicit a Ca(2+) response [6].
• The mRNA expression levels of GPR39 were negatively correlated to fasting glucose concentrations (r = -0.581, P = 0.023), while exhibiting a positive correlation to adiponectin mRNA expression levels (r = 0.674, P = 0.006) [1].
• In vivo experiments in rats demonstrated that GPR39 is up-regulated in adipose tissue during fasting and in response to streptozotocin treatment, although its expression is kept constant in the liver from the same animals [9].

Other interactions of GPR39

• The ligand-binding and functional properties of GPR38 and GPR39 remain to be determined [4].
• Results Obese T2DM patients exhibited significantly lower GPR39 expression levels compared to lean (P = 0.016) and obese normoglycaemic subjects (P = 0.008), while no differences between lean and obese normoglycaemic patients were observed [1].

Analytical, diagnostic and therapeutic context of GPR39

• Real-time RT-PCR analyses were performed to quantify transcript levels of GPR39 and adiponectin [1].

References